Mitochondrial DNA (mtDNA) deletions are a major cause of chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS). We analyzed single mtDNA deletions in 11 CPEO and one KSS patients by means of Southern blot and long polymerase chain reaction (PCR) assays. The deletion sizes ranged from 3.4 kb to 6.9 kb whereas the heteroplasmy level varied from 18.8% to 85.5%. Two unique deletions sized 4320 bp and 4717 bp were found. This study represents the first genetic screen of mtDNA disorders in Malaysia, and it follows the data seen in other published reports on CPEO and KSS genetic aetiology.

Issues pertaining to the diagnosis and management of inborn errors of metabolism (IEM) in Malaysia included low awareness of atypical and variable presentations in IEMs leading to delayed diagnosis or treatment, absence of reliable population data on IEMs and involvement of multiple siblings in the same family due to consanguinity. The importance of careful family history taking and genetic counselling are emphasised. Selected testing of ill infants and children for IEM yielded a positive 2% (264/13,500) results for IEMs in Malaysia. Out of the 264 patients, the spectrum of IEMs in Malaysia included organic acidurias (98), aminoacidopathies (78), urea cycle defects (54), neurotransmitter conditions (12) and lysosomal disorders, mainly mucopolysaccharidosis (14). Confirmatory studies of IEMs are an important aspect of management of IEMs. There is a need for more metabolic specialists and funding for diagnosis and treatment of IEMs in Malaysia. Long-term care issues and cost-effectiveness of IEM therapy, supportive and preventive aspects will need further studies in Malaysia.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant, Newborn ; Malaysia ; epidemiology ; Male ; Metabolism, Inborn Errors ; diagnosis ; epidemiology ; therapy

Dystrophinopathies commonly present as Duchenne or Becker muscular dystrophy but rare, unusual phenotypes have also been described. We have identifi ed three Malaysian boys with an unusual form of dystrophinopathy, presenting with exercise-induced cramps and myoglobinuria, but with no apparent muscle weakness. Immunohistochemistry for dystrophin and genetic analysis confi rmed the diagnosis. The frequency of this phenotype is unknown but there have been several case reports. Consistent with these reports, we also found that two of our patients had deletions in the rod domain of dystrophin, which has been suggested to be associated with this unusual manifestation

Child ; Humans ; Lung Diseases, Interstitial/diagnostic imaging*